The WWAMI RCE will develop a strong program of basic research, education, and training in biodefense and emerging infectious diseases with a focus on Gram-negative pathogens. The objectives are: 1. Development of a regional program supported by modem biotechnology platforms, including proteomics, genomics, and bioinformatics dedicated to studying the biology and pathogenesis of Gram-negative bacterial agents of relevance to biodefense and emerging infectious diseases. The WWAMI RCE will initially focus on Yersinia pestis (YP), Francisella tularensis (FT), and Burkholderia pseudomallei (BP). 2. Development of a regional program to understand in greater detail the pathophysiology of airway infection and inflammation by Gram-negative pathogens. Animal models of airway infection will be utilized, including non-human primates and rodents. 3. Development of a regional program that will study differences in human susceptibility to Gram-negative bacterial agents of relevance to biodefense and emerging infectious diseases. Initial studies will define variability in the response of normal humans of varying genetic backgrounds to LPS from YP, FT, and synthetic LPS derived compounds. 4. Translate information obtained into preclinical testing of vaccine candidates and therapeutics that can be useful in protection against Gram-negative agents of relevance to biodefense and emerging infectious diseases. The initial focus will be on the development of vaccines for YP and the use of synthetic LPS derived compounds as adjuvants and innate immune stimulators that broadly protect against a variety of infectious agents. 5. Utilize the extensive WWAMI regional program in education and training to recruit new investigators and educate trainees about the field of biodefense and emerging infectious diseases. 5. Development of a regional plan to interface with the regional public health network to utilize WWAMI RCE resources in a national emergency.